Could Small Neurotoxins-Peptides be Expressed during SARS-CoV-2 Infection?

: SARS-CoV-2 pathogenesis has been recently extended to human central nervous system (CNS), in addition to nasopharyngeal truck, eye, lung and gut. The recent literature highlights that some SARS-CoV-2 spike glycoprotein regions homologous to neurotoxin-like peptides might bind to human nicotinic Acetyl-Choline Receptors (nAChRs). Spike-nAChR interaction can probably cause dysregulation of CNS and cholinergic anti-inflammatory pathways and uncontrolled immune-response, both associated to a severe COVID-19 pathophysiology. Herein, we hypothesize that inside the Open Reading Frame (ORF) region of spike glycoprotein, the RNA polymerase can translate small neurotoxic peptides by means of a “jumping mechanism” already demonstrated in other coronaviruses. These small peptides can bind the snAChRs instead of Spike glycoproteins. A striking homology occurred between these small peptides observed by sequence retrieval and proteins alignment. Acting as nAChRs antagonists, these small peptides (conotoxins) could be the explanation for the extrapulmonary clinical manifestations (neurological, hemorrhagic and thrombotic expressions, the prolonged apnea, the cardiocirculatory collapse, the heart arrhythmias, the ventricular tachycardia, the body temperature alteration, the electrolyte K+ imbalance and finally the significant reduction of butyryl cholinesterase (BuChE) plasma levels, as observed in COVID-19 patients. Several factors might induce the expression of these small peptides, including microbiota. The main hypothesis regarding the presence of these small peptides opens a new scenario on the etiology of COVID-19 clinical symptoms observed so far, including the neurological manifestations.

Prolonged apnea after ECT in organophosphorus poisoning – the need to redefine norms

Background Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency ward and the ICU. OP compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a unusual case of OP poisoning (OPP) in which prolonged apnea ensued in a patient of severe depression following MECT (modified electroconvulsive therapy) in which suxamethonium was used as muscle relaxant, in whom we were cautious of the side-effect of prior organophosphorus poisoning. Since the cases of OPP are very high worldwide, a thorough knowledge of the interaction of the action of the drug and the receptors on which it acts takes pride of place. This article highlights the nuances in the field of psychiatry and anaesthesia in diagnosis and management of prolonged apnea after ECT. Case presentation A 53/F patient consumed OP 38 days prior to MECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of < 0.3 mg/kg, the patient remained apneic for 3 h. Suxamethionum apnea was managed with elective ventilation. After recovery, patient had no residual effect. Subsequently her pseudocholinesterase levels were done which were found to be very low. Conclusion This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure. In strong suspects dibucaine number and fluoride number also needs to be estimated.

Mapping the functional brain state of a world champion freediver in static dry apnea

Voluntary apnea showcases extreme human adaptability in trained individuals like professional free divers. We evaluated the physiological and psychological adaptation and the functional cerebral changes using EEG and fMRI to 6.5 minutes of dry static apnea performed by a world champion free diver. Compared to resting state at baseline, apnea was characterized by increased EEG power and functional connectivity in the alpha band, along with decreased delta band connectivity. fMRI connectivity was increased within the DMN and visual areas but decreased in pre- and postcentral cortices. While these changes occurred in regions overlapping with cerebral signatures of several meditation practices, they also display some unique features that suggest an altered somatosensory integration. As suggested by the self-reported phenomenology, these findings could reflect the ability of elite free divers to create a (functional) dissociation between the body and the mind when performing prolonged apnea.

Prolonged Apnea After Ect In Organophosphorus Poisoning – The Need To Redefine Norms

Background:Organophosphorous (OP) compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a case in which prolonged apnea ensued in a patient of severe depression following ECT in which suxamethonium was used as muscle relaxant, in whom we were cautious of the effect of organophosphorus poisoning.Case Presentation 53/F patient consumed OP 38 days prior to ECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of <0.3mg/kg, the patient remained apneic for 3 hours. Subsequently her pseudocholinesterase levels were also found to be very low.Conclusion This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure.

Personalized pediatric anesthesia and pain management: problem-based review

Pharmacogenetics, the genetic influence on the interpersonal variability in drug response, has enabled tailored pharmacotherapy and emerging ‘personalized medicine.’ Although oncology spearheaded the clinical implementation of personalized medicine, other specialties are rapidly catching up. In anesthesia, classical examples of genetically mediated idiosyncratic reactions have been long known (e.g., malignant hyperthermia and prolonged apnea after succinylcholine). The last two decades have witnessed an expanding body of pharmacogenetic evidence in anesthesia. This review highlights some of the prominent pharmacogenetic associations studied in anesthesia and pain management, with special focus on pediatric anesthesia.

Anesthesia Related Complications of Gastrointestinal Endoscopies; A Retrospective Descriptive Study

BACKGROUND Gastrointestinal endoscopic procedures are widely used for diagnostic and therapeutic measures. Analgesia and sedation/anesthesia are inseparable parts of these studies and their related complications are inevitable. METHODS In a retrograde descriptive study in Shahid Beheshti Hospital, affiliated to Qom University of Medical Sciences, Qom, Iran from March 2013 to March 2017, we gathered information regarding common anesthesia related complications and analyzed them. RESULTS 44659 procedures were performed during the study period and records of 21342 men (47.79%) and 23317 women (52.21%) were evaluated. Hemodynamic instability (9998; 22.39%), dysrhythmia (1600; 3.58%), desaturation (608; 1.36%), prolonged apnea (34; 0.08%), aspiration (43; 0.10%), postoperative nausea and vomiting (PONV) (636; 1.42%), headache (106; 0.24%), delirium (51; 0.11%), aphasia (1; 0.00%), masseter muscle spasm (1; 0.01%), myocardial infarction (2; 0.00%), and death (5; 0.01%) were seen in the patients. CONCLUSION Sedation/anesthesia is enough safe in gastrointestinal endoscopic procedures to enhance the patients’ satisfaction and cooperation. If anesthesia with spontaneous breathing and unsecure airway is selected for this purpose, vigilance of anesthesia provider will be the key element of uneventful and safe procedure.

Pharmacogenomic considerations for medications in the perioperative setting

Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea, respiratory depression, inadequate analgesia), leading to an increased understanding of genetic susceptibilities underlying these risks. Pharmacogenomic information is increasingly being utilized in certain areas of medicine. Despite this, routine preoperative genetic screening to inform medication risk is not yet standard practice. In this review, we assess the current readiness of pharmacogenomic information for clinical consideration for several common perioperative medications, including description of key pharmacogenes, pharmacokinetic implications and potential clinical outcomes. The goal is to highlight medications for which emerging or considerable pharmacogenomic information exists and identify areas for future potential research.

Novel clinical features of nonconvulsive status epilepticus

Nonconvulsive status epilepticus (NCSE) has rapidly expanded from classical features such as staring, repetitive blinking, chewing, swallowing, and automatism to include coma, prolonged apnea, cardiac arrest, dementia, and higher brain dysfunction, which were demonstrated mainly after the 2000s by us and other groups. This review details novel clinical features of NCSE as a manifestation of epilepsy, but one that is underdiagnosed, with the best available evidence. Also, we describe the new concept of epilepsy-related organ dysfunction (Epi-ROD) and a novel electrode and headset which enables prompt electroencephalography.